Teclistamab Provides Substantial Clinical Benefit Over Real-World Physician’s Choice in Triple-Class Exposed R/R Myeloma

Amrita Krishnan, MD

Teclistamab was found to have improved effectiveness in terms of progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS) vs real-world physician’s choice of therapy in patients with triple-class exposed relapsed/refractory multiple myeloma who received at least 3 prior lines of therapy, according to data from a recent study.¹

For the research, individual patient-level data were collected from the phase 1/2 MajestTEC-1 trial (NCT04557098) and were compared with an external control arm that utilized data from patients in the nationwide de-identified electronic health record-derived Flatiron Health Multiple Myeloma cohort database.

Outcomes were assessed as time-to-event data utilizing inverse probability of treatment weighting (IPTW) adjusted Kaplan-Meier estimates and a weighted Cox proportional hazards model to estimate the hazard ratio (HR) and its 95% confidence interval (CI).

The findings from the base case analysis, which were presented during the 2022 ASCO Annual Meeting, showed that the median OS with teclistamab was 18.3 months vs 13.8 months in the unweighted Flatiron cohort and 14.6 months in the weighted flatiron cohort (unadjusted HR, 0.67; 95% CI, 0.47-0.95; best case HR, 0.73; 95% CI, 0.50-1.07; P = .1084).

The median PFS with teclistamab was 10.05 months vs 3.91 months in the unweighted cohort and 3.55 months in the weighted cohort (unadjusted HR, 0.42; 95% CI, 0.32-0.56; best case HR, 0.43; 95% CI, 0.32-0.57; P < .0001). Moreover, the median TTNT was not yet reached with teclistamab vs 5.19 months in the unweighted cohort and 4.90 months in the weighted cohort (unadjusted HR, 0.38; 95% CI, 0.28-0.52; best case HR, 0.39; 95% CI, 0.28-0.53; P < .0001).

“In the absence of head-to-head trials comparing teclistamab with other treatments, this study demonstrates that teclistamab offers substantial clinical benefit over real-world physician’s choice of therapy in patients with triple-class exposed relapsed/refractory multiple myeloma who received 3 or more prior lines of therapy,” Amrita Krishnan, MD, director of the Judy and Bernard Briskin Center for Multiple Myeloma Research; professor in the Department of Hematology & Hematopoietic Cell Transplantation; and chief of the Division of Multiple Myeloma at City of Hope, and colleagues, wrote in a poster on the data.

Patients who have relapsed or refractory multiple myeloma are known to have a poor prognosis and to cycle through proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies. The T-cell–redirecting bispecific antibody, teclistamab, is currently being explored in patients with relapsed or refractory disease who previously received at least 3 lines of therapy and who were triple-class exposed, as part of the MajesTEC-1 trial.

For the study presented during the meeting, investigators sought to compare the effectiveness of the agent with that of physician’s choice of therapy from a real-world database.

The data collected from MajesTEC-1 included information on patients who received teclistamab at a weekly dose of 1.5 mg/kg (n = 150) with a cutoff date of November 9, 2021. The external control arm was created by using information from patients within the Flatiron database who had 2 or more documented clinical visits on, or after, January 1, 2011.

Those eligible to participate on MajesTEC-1 (n = 150) had to be triple-class exposed, have received 3 or more prior lines of therapy, have an ECOG performance status less than 2, creatinine of 1.5 mg/dL or less, hemoglobin of greater than 8 g/dL, and have experienced disease progression within 12 months of their most recent line of therapy.

Those included in the external control arm (n = 420) had to be triple-class exposed, have received at least 1 treatment following triple-class exposure, have received at least 3 prior lines of therapy, and meet the same performance status, creatinine, and hemoglobin criteria as those included on MajesTEC. These patients also needed to have experienced progressive disease within 1 year of their most recent line of therapy, and they needed to have data available with regard to OS, PFS, and TTNT.

Investigators used IPTW with average treatment effect on the treated population to adjust for imbalances in baseline covariates of prognostic significance (base case), such as refractory status, time to disease progression on last line of therapy received, cytogenetic risk, International Staging System stage, number of prior lines of therapy received, time since diagnosis, age, and hemoglobin.

Patients were considered to be refractory if they had discontinued the drug of interest within 60 days and started treatment with a different drug in the next line of therapy or started treatment with a new drug within 60 days following the completion of their prior treatment.

Investigators also conducted a sensitivity analysis that weighted patients on prior stem cell transplant, ECOG performance status, race, sex, and type of multiple myeloma, as well as the base case variables. Data from this analysis proved to be consistent with what had been observed in the base case analysis.

Specifically, data from the sensitivity analysis showed that with regard to OS, the OS with teclistamab was 18.3 months (95% CI, 18.3-NR) vs 13.2 months (95% CI, 10.6-18.7) with physician’s choice of treatment (HR, 0.67; 95% CI, 0.43-1.05; P = .0829). The PFS with teclistamab was 10.05 months (95% CI, 8.05-NR) vs 3.38 months (95% CI, 3.02-4.30) with physician’s choice (HR, 0.42; 95% CI, 0.30-0.58; P < .0001). The TTNT was not reached (95% CI, 10.81-NR) with teclistamab vs 4.40 months (95% CI, 3.52-5.36) with physician’s choice of therapy (HR, 0.39; 95% CI, 0.28-0.55; P < .0001).

Reference

Krishnan A, Nooka AK, Chari A, et al. Comparative effectiveness of teclistamab versus real-world treatments for patients with triple-class exposed (TCE), relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2022;40(suppl 16):8036. doi:10.1200/JCO.2022.40.16_suppl.8036